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The Effect of Combination of Mosapride and DPP-4 Inhibitor on Plasma Concentration of Incretin Hormones

Phase 4
Completed
Conditions
Diabetes Mellitus, Type 2
Interventions
Registration Number
NCT02180334
Lead Sponsor
Seoul National University Hospital
Brief Summary

The aim of this study is to investigate the effects of combined administration of mosapride as modulator of gastrointestinal motility and DPP-4 inhibitor on secretion of gut hormone such as glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP), and oral glucose tolerance. Additionally, change in lipid profile and insulin secretion will be also assessed.

Detailed Description

This is randomized, double-blind, placebo-controlled, cross-over study. After screening and enrollment, participants will take 5 mg of linagliptin once a day for one week of run-in period (Day 1 to Day 7). Randomization will be done on Day 8 to assign the participants to either mosapride arm or placebo arm. If a subject is assigned to mosapride arm, mixed meal tolerance test (MMTT) will be performed after taking mosapride with linagliptin. If a subject is assigned to placebo arm, he/she will take placebo instead of mosapride before MMTT. On Day 9, all subjects will be crossed over to the other arm and MMTT will proceed with medication depending on their arms. Gastric emptying time measurement with paracetamol will be done along with MMTT. Plasma incretin hormone levels in two arms will be compared.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
12
Inclusion Criteria
  • type 2 diabetes mellitus
  • BMI < 35 kg/m2
  • HbA1c 6.5~8.0% for whom is on lifestyle modification only, 6.0~8.0% for whom is taking oral antidiabetic drug(s).
  • on lifestyle modification or oral antidiabetic therapy (sulfonylurea, biguanides, thiazolidinediones, alpha-glucosidase inhibitors, and DPP-4 inhibitors)
  • Who read and signed the informed consent agreement
Exclusion Criteria
  • chronic disease(s) requiring medication other than diabetes mellitus
  • type 1 diabetes mellitus or history of diabetic ketoacidosis
  • on insulin therapy or requiring insulin therapy
  • history of gastrointestinal surgery excluding appendectomy, hernia repair and hemorrhoid surgery
  • serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) to be more than 2.5 times above the upper limit of normal
  • estimated glomerular filtration rate to be less than 50 mL/min/1.73m2
  • genetic disorders associated with digestion and absorption such as galactose intolerance, Lapp lactase deficiency, and glucose-galactose malabsorption
  • history of hypersensitivity including anaphylaxis and angioedema to mosapride citrate, linagliptin, or paracetamol (acetaminophen)
  • history of asthma associated with aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs)
  • currently taking drugs that can prolong QT interval, including procainamide, quinidine, flecainide, sotalol, tricyclic antidepressants
  • currently taking anticholinergics such as atropine sulfate, scopolamine butylbromide
  • child-bearing or lactating women
  • women in reproductive age who disagree with contraception with proper method or urine pregnancy test during the study period

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
MosaprideAcetaminophen (paracetamol)* Mosapride citrate 5 mg (Gasmotin®): 1 tablet (5 mg) will be administered 1 hour before MMTT. * Linagliptin 5 mg (Trajenta®): 1 tablet (5 mg) per day should be taken for 7 days during run-in period. 1 tablet (5 mg) will be administered 1 hour before MMTT. * Acetaminophen 500 mg (Tylenol®): 3 tablets (1500 mg) will be administered at once with the mixed meal for calculating gastric emptying time.
ControlAcetaminophen (paracetamol)* Placebo drug: 1 tablet will be administered 1 hour before MMTT. * Linagliptin 5 mg (Trajenta®): 1 tablet (5 mg) per day should be taken for 7 days during run-in period. 1 tablet (5 mg) will be administered 1 hour before MMTT. * Acetaminophen 500 mg (Tylenol®): 3 tablets (1500 mg) will be administered at once with the mixed meal for calculating gastric emptying time.
MosaprideMosapride citrate* Mosapride citrate 5 mg (Gasmotin®): 1 tablet (5 mg) will be administered 1 hour before MMTT. * Linagliptin 5 mg (Trajenta®): 1 tablet (5 mg) per day should be taken for 7 days during run-in period. 1 tablet (5 mg) will be administered 1 hour before MMTT. * Acetaminophen 500 mg (Tylenol®): 3 tablets (1500 mg) will be administered at once with the mixed meal for calculating gastric emptying time.
ControlLinagliptin* Placebo drug: 1 tablet will be administered 1 hour before MMTT. * Linagliptin 5 mg (Trajenta®): 1 tablet (5 mg) per day should be taken for 7 days during run-in period. 1 tablet (5 mg) will be administered 1 hour before MMTT. * Acetaminophen 500 mg (Tylenol®): 3 tablets (1500 mg) will be administered at once with the mixed meal for calculating gastric emptying time.
MosaprideLinagliptin* Mosapride citrate 5 mg (Gasmotin®): 1 tablet (5 mg) will be administered 1 hour before MMTT. * Linagliptin 5 mg (Trajenta®): 1 tablet (5 mg) per day should be taken for 7 days during run-in period. 1 tablet (5 mg) will be administered 1 hour before MMTT. * Acetaminophen 500 mg (Tylenol®): 3 tablets (1500 mg) will be administered at once with the mixed meal for calculating gastric emptying time.
Primary Outcome Measures
NameTimeMethod
Area under the curve (AUC) of plasma total GLP-1 levels0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)

AUC of plasma total GLP-1 levels during MMTT

Secondary Outcome Measures
NameTimeMethod
Area under the curve (AUC) of serum triglyceride levels0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)

AUC of serum triglyceride levels during MMTT

Area under the curve (AUC) of plasma glucose levels0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)

AUC of plasma glucose levels during MMTT

Area under the curve (AUC) of plasma insulin levels0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)

AUC of plasma insulin levels during MMTT

Area under the curve (AUC) of plasma total GIP levels0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)

AUC of plasma total GIP levels during MMTT

Area under the curve (AUC) of plasma C-peptide levels0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)

AUC of plasma C-peptide levels during MMTT

Area under the curve (AUC) of plasma active GLP-1 levels0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)

AUC of plasma active GLP-1 levels during MMTT

Area under the curve (AUC) of serum nonesterified fatty acid (NEFA) levels0, 15, 30, 60, 90, 120, 150, 180 min after taking mixed meal (manufactured)

AUC of serum NEFA levels during MMTT

Trial Locations

Locations (1)

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

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